Safety Profile, Pharmacokinetics, and Pharmacodynamics of Siplizumab, A Humanized Anti-CD2 Monoclonal Antibody, in Renal Allograft Recipients

T. L. Pruett, R. W. McGory, F. H. Wright, M. D. Pescovitz, H. Yang, J. B. McClain

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: We report the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of siplizumab, a humanized IgG1 anti-CD2 monoclonal antibody and potential agent for preventing renal allograft rejection, in a phase 1 study in renal allograft recipients. Methods: Subjects on conventional immunosuppressive regimens received 2 infusions (4-6 and 60-72 hours postsurgery) of siplizumab (0.012, 0.06, or 0.12 mg/kg per dose). Adverse events (AEs) were recorded for 33 days. Serum siplizumab concentrations were measured and PD was assessed by flow cytometry and NK in vitro cytotoxicity. Results: Thirteen renal allograft recipients were enrolled. Two patients had mild infusion reactions with single temperature elevations of 38.2°C and 38.6°C, respectively. Eight patients had siplizumab-related AEs: lymphopenia (7 patients), anemia (3), chills (2), and nausea (2). Mean natural killer (NK) cell cytotoxicity decreased after the first dose, but exceeded pretreatment values by day 33 in all patients. No anti-siplizumab antibodies were detected. The 0.012 mg/kg group did not achieve quantifiable siplizumab serum concentrations. By the second dose, mean peak concentrations were 958 ng/mL, with mean T 1/2 of 29 hours, in the 0.06 mg/kg group, and 2870 ng/mL, with mean T 1/2 of 49 hours, in the 0.12 mg/kg group. Mean total lymphocyte and CD2 + lymphocyte counts declined after the first infusion and rose by day 8 in all groups despite a second infusion of siplizumab. Lymphocyte counts returned to pretreatment levels by day 60. Conclusion: Siplizumab exhibited an acceptable safety profile in this study. Detectable siplizumab concentrations were maintained for 3 days after the second dose at the 2 highest dose levels.

Original languageEnglish (US)
Pages (from-to)3655-3661
Number of pages7
JournalTransplantation proceedings
Volume41
Issue number9
DOIs
StatePublished - Nov 1 2009

Fingerprint

Allografts
Pharmacokinetics
Monoclonal Antibodies
Kidney
Safety
Lymphocyte Count
Renal Agents
siplizumab
Chills
Lymphopenia
Immunosuppressive Agents
Serum
Natural Killer Cells
Nausea
Anemia
Anti-Idiotypic Antibodies
Flow Cytometry
Immunoglobulin G
Lymphocytes
Temperature

Cite this

Safety Profile, Pharmacokinetics, and Pharmacodynamics of Siplizumab, A Humanized Anti-CD2 Monoclonal Antibody, in Renal Allograft Recipients. / Pruett, T. L.; McGory, R. W.; Wright, F. H.; Pescovitz, M. D.; Yang, H.; McClain, J. B.

In: Transplantation proceedings, Vol. 41, No. 9, 01.11.2009, p. 3655-3661.

Research output: Contribution to journalArticle

Pruett, T. L. ; McGory, R. W. ; Wright, F. H. ; Pescovitz, M. D. ; Yang, H. ; McClain, J. B. / Safety Profile, Pharmacokinetics, and Pharmacodynamics of Siplizumab, A Humanized Anti-CD2 Monoclonal Antibody, in Renal Allograft Recipients. In: Transplantation proceedings. 2009 ; Vol. 41, No. 9. pp. 3655-3661.
@article{a2a4ed93954044a8ad67517932abfaaf,
title = "Safety Profile, Pharmacokinetics, and Pharmacodynamics of Siplizumab, A Humanized Anti-CD2 Monoclonal Antibody, in Renal Allograft Recipients",
abstract = "Background: We report the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of siplizumab, a humanized IgG1 anti-CD2 monoclonal antibody and potential agent for preventing renal allograft rejection, in a phase 1 study in renal allograft recipients. Methods: Subjects on conventional immunosuppressive regimens received 2 infusions (4-6 and 60-72 hours postsurgery) of siplizumab (0.012, 0.06, or 0.12 mg/kg per dose). Adverse events (AEs) were recorded for 33 days. Serum siplizumab concentrations were measured and PD was assessed by flow cytometry and NK in vitro cytotoxicity. Results: Thirteen renal allograft recipients were enrolled. Two patients had mild infusion reactions with single temperature elevations of 38.2°C and 38.6°C, respectively. Eight patients had siplizumab-related AEs: lymphopenia (7 patients), anemia (3), chills (2), and nausea (2). Mean natural killer (NK) cell cytotoxicity decreased after the first dose, but exceeded pretreatment values by day 33 in all patients. No anti-siplizumab antibodies were detected. The 0.012 mg/kg group did not achieve quantifiable siplizumab serum concentrations. By the second dose, mean peak concentrations were 958 ng/mL, with mean T 1/2 of 29 hours, in the 0.06 mg/kg group, and 2870 ng/mL, with mean T 1/2 of 49 hours, in the 0.12 mg/kg group. Mean total lymphocyte and CD2 + lymphocyte counts declined after the first infusion and rose by day 8 in all groups despite a second infusion of siplizumab. Lymphocyte counts returned to pretreatment levels by day 60. Conclusion: Siplizumab exhibited an acceptable safety profile in this study. Detectable siplizumab concentrations were maintained for 3 days after the second dose at the 2 highest dose levels.",
author = "Pruett, {T. L.} and McGory, {R. W.} and Wright, {F. H.} and Pescovitz, {M. D.} and H. Yang and McClain, {J. B.}",
year = "2009",
month = "11",
day = "1",
doi = "10.1016/j.transproceed.2009.06.226",
language = "English (US)",
volume = "41",
pages = "3655--3661",
journal = "Transplantation Proceedings",
issn = "0041-1345",
publisher = "Elsevier USA",
number = "9",

}

TY - JOUR

T1 - Safety Profile, Pharmacokinetics, and Pharmacodynamics of Siplizumab, A Humanized Anti-CD2 Monoclonal Antibody, in Renal Allograft Recipients

AU - Pruett, T. L.

AU - McGory, R. W.

AU - Wright, F. H.

AU - Pescovitz, M. D.

AU - Yang, H.

AU - McClain, J. B.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - Background: We report the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of siplizumab, a humanized IgG1 anti-CD2 monoclonal antibody and potential agent for preventing renal allograft rejection, in a phase 1 study in renal allograft recipients. Methods: Subjects on conventional immunosuppressive regimens received 2 infusions (4-6 and 60-72 hours postsurgery) of siplizumab (0.012, 0.06, or 0.12 mg/kg per dose). Adverse events (AEs) were recorded for 33 days. Serum siplizumab concentrations were measured and PD was assessed by flow cytometry and NK in vitro cytotoxicity. Results: Thirteen renal allograft recipients were enrolled. Two patients had mild infusion reactions with single temperature elevations of 38.2°C and 38.6°C, respectively. Eight patients had siplizumab-related AEs: lymphopenia (7 patients), anemia (3), chills (2), and nausea (2). Mean natural killer (NK) cell cytotoxicity decreased after the first dose, but exceeded pretreatment values by day 33 in all patients. No anti-siplizumab antibodies were detected. The 0.012 mg/kg group did not achieve quantifiable siplizumab serum concentrations. By the second dose, mean peak concentrations were 958 ng/mL, with mean T 1/2 of 29 hours, in the 0.06 mg/kg group, and 2870 ng/mL, with mean T 1/2 of 49 hours, in the 0.12 mg/kg group. Mean total lymphocyte and CD2 + lymphocyte counts declined after the first infusion and rose by day 8 in all groups despite a second infusion of siplizumab. Lymphocyte counts returned to pretreatment levels by day 60. Conclusion: Siplizumab exhibited an acceptable safety profile in this study. Detectable siplizumab concentrations were maintained for 3 days after the second dose at the 2 highest dose levels.

AB - Background: We report the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of siplizumab, a humanized IgG1 anti-CD2 monoclonal antibody and potential agent for preventing renal allograft rejection, in a phase 1 study in renal allograft recipients. Methods: Subjects on conventional immunosuppressive regimens received 2 infusions (4-6 and 60-72 hours postsurgery) of siplizumab (0.012, 0.06, or 0.12 mg/kg per dose). Adverse events (AEs) were recorded for 33 days. Serum siplizumab concentrations were measured and PD was assessed by flow cytometry and NK in vitro cytotoxicity. Results: Thirteen renal allograft recipients were enrolled. Two patients had mild infusion reactions with single temperature elevations of 38.2°C and 38.6°C, respectively. Eight patients had siplizumab-related AEs: lymphopenia (7 patients), anemia (3), chills (2), and nausea (2). Mean natural killer (NK) cell cytotoxicity decreased after the first dose, but exceeded pretreatment values by day 33 in all patients. No anti-siplizumab antibodies were detected. The 0.012 mg/kg group did not achieve quantifiable siplizumab serum concentrations. By the second dose, mean peak concentrations were 958 ng/mL, with mean T 1/2 of 29 hours, in the 0.06 mg/kg group, and 2870 ng/mL, with mean T 1/2 of 49 hours, in the 0.12 mg/kg group. Mean total lymphocyte and CD2 + lymphocyte counts declined after the first infusion and rose by day 8 in all groups despite a second infusion of siplizumab. Lymphocyte counts returned to pretreatment levels by day 60. Conclusion: Siplizumab exhibited an acceptable safety profile in this study. Detectable siplizumab concentrations were maintained for 3 days after the second dose at the 2 highest dose levels.

UR - http://www.scopus.com/inward/record.url?scp=71749100822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71749100822&partnerID=8YFLogxK

U2 - 10.1016/j.transproceed.2009.06.226

DO - 10.1016/j.transproceed.2009.06.226

M3 - Article

C2 - 19917362

AN - SCOPUS:71749100822

VL - 41

SP - 3655

EP - 3661

JO - Transplantation Proceedings

JF - Transplantation Proceedings

SN - 0041-1345

IS - 9

ER -